Concurrent increases in post-pacing action potential duration and contractility predict occurrence of ventricular arrhythmia

Chih Min Liu, Feng Zhi Lin, Yao Chang Chen, Yung Kuo Lin, Yen Yu Lu, Cheng I. Wu, Satoshi Higa, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD90, p < 0.001) and contractility (ΔContractility, p = 0.003) compared with group 2. Triggered VT episodes were common (72.7%) in cases with a ΔAPD90 > 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD90 < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na+–Ca2+ exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.

Original languageEnglish
JournalPflugers Archiv European Journal of Physiology
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • Action potential depolarization
  • Contractility
  • Na–Ca exchanger inhibitor
  • Ventricular arrhythmias

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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